POS0177 HETEROGENOUS CARTILAGE DAMAGE SEEN ON MRI AMONG KNEES WITH KELLGREN-LAWRENCE 2 &amp; 3 OSTEOARTHRITIS: WHAT ARE THE IMPLICATIONS FOR CLINICAL TRIALS?
Authors: M. Jarraya, F. Roemer, E. Ashbeck, J. Lynch, C. K. Kwoh, A. Guermazi
Journal: Annals of the Rheumatic Diseases (2022)

Background The most recent update of the Global Burden of Disease figures (GBD 2013) estimated that 242 million people were living in the world with symptomatic and activity-limiting OA of the hip and/or knee. Many potential disease-modifying osteoarthritis drugs (DMOADs) have been investigated, but to date no DMOADs that slow or stop disease progression have been approved by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA). A potential reason for the lack of demonstrated efficacy may be reliance on radiographs for defining structural inclusion and exclusion criteria for clinical trials, such as use of joint space width and Kellgren-Lawrence (KL) grade as surrogates for cartilage damage. Objectives To estimate the distribution of cartilage damage seen on knee MRI in a sample of knees with radiographic KL 2 and 3 OA that would potentially qualify for a DMOAD trial. Methods We selected knees from the Osteoarthritis Initiative (OAI), a longitudinal cohort study of knees with or at risk of developing symptomatic radiographic OA, that met common structural inclusion criteria for DMOAD trial enrollment at OAI baseline: knees with radiographs centrally graded as KL 2 or 3 and medial minimum joint space width (mJSW) ≥ 1.5mm. A musculoskeletal radiologist with 10 years of experience in semi-quantitative MRI assessment scored knee cartilage damage in the medial and lateral tibiofemoral and patellofemoral compartments using WORMS (Whole-Organ Magnetic Resonance Imaging Score). Coronal intermediate weighted (IW) TSE and sagittal fat-suppressed IW TSE sequences on 3T MRI were used. The WORMS cartilage scores, which are based on both the extent and depth of cartilage damage, were collapsed into 4 categories: no cartilage damage (WORMS 0 and 1), focal partial or full-thickness (PT/FT) cartilage damage (WORMS 2 and 2.5), diffuse partial thickness (PT) cartilage damage (WORMS 3 and 4), and diffuse full-thickness (FT) cartilage damage (WORMS 5 and 6). We estimated the prevalence of each category of cartilage damage in KL2 and KL3 knees; 95% confidence intervals (CI) accounted for clustering at the participant-level since some participants contributed two knees to the analysis. Results We identified 2,372 participants contributing 3,446 knees with radiographic OA (KL 2 and 3) and medial mJSW ≥ 1.5mm. There were 2,318 KL2 knees and 1,128 KL3 knees. The distribution of cartilage damage in each compartment by KL grade is presented in Table 1. We found no cartilage damage in any compartments in 9.8% (95%CI: 8.5, 11.1) of KL2 knees and 2.0% (95%CI: 1.1, 2.9) of KL3 knees. Cartilage damage was absent in the medial tibiofemoral compartment in 52.4% (95%CI: 50.1, 54.6) of KL2 knees, and 14.4% (95%CI: 12.2, 16.6) of KL3 knees, versus 61% (95%CI: 58.8, 63.2) of KL2 knees and 53.6% (95%CI: 50.4, 56.7) of KL3 knees in the lateral compartment. When medial and lateral compartments were combined, cartilage damage was absent in 34.8% (95%CI: 32.7, 36.9) of the KL2 knees, and 4.3% (95%CI: 3.0, 5.5) of the KL3 knees. Diffuse FT cartilage lesions in the medial compartment were found in 6.1% (95%CI: 5.0, 7.1) of KL2 knees and 42.5% (95%CI: 39.4, 45.6) of KL3 knees. Conclusion MRI screening prior to clinical trial enrollment may identify a substantial percentage of knees with normal cartilage, as well as knees with diffuse FT cartilage lesions that may not be responsive to DMOADs, depending on the mode of action of a given pharmacological compound. Disclosure of Interests Mohamed Jarraya: None declared, Frank Roemer Shareholder of: Boston Imaging Core Lab, Consultant of: California Institute of Biomedical Research, Erin Ashbeck: None declared, John Lynch: None declared, C. Kent Kwoh Consultant of: Novartis, Regeneron, LG Chem, Kolon Tissue Gene, Avalor, Grant/research support from: Pfizer, Lilly, Cumberland, Ali Guermazi Shareholder of: Stock options in BICL, Consultant of: Pfizer, TissueGene, MerckSerono, Regeneron, Novartis, AstraZeneca